PRA in the English Springer Spaniel

CORD1 (RPGRIP1) Recruitment Study in 2016

It is exciting to report that geneticists at the Animal Health Trust have recently identified a new candidate mutation for PRA in a different breed (follow link to see more information on this in the Miniature Long-Haired Dachshund). This has been acknowledged as a potential “modifying” mutation that determines whether dogs affected for the CORD1 mutation will develop early onset PRA. We want to investigate whether this modifying mutation is present in the English Springer Spaniel breed at all. Additional potential candidate mutations are being identified as our research into PRA progresses, and these interesting variants need investigating further too.

Sample recruitment for this study closed in June 2016 and we're pleased to report that we received a fantastic 925 DNA samples from English Springer Spaniels. That's 99% of our target and enough samples for us to progress the research. A huge thank you to all who have participated in the study, we couldn't complete the research without the DNA samples so your contribution really is vital.

As we are trying to determine if there are other genetic variants that cause PRA in English Springer Spaniels, these samples will also be useful for further validation of any new variants found, which could help us develop modified, and more effective, DNA tests for PRA in the future.

CORD1 Research Results

All confidential CORD1 DNA research results were emailed to owners who provided an email address on their dog’s submission form at the beginning of September 2016.

PRA research and DNA testing so far

PRA is a blinding disease for which there is no treatment, affecting over 100 breeds of dog. The English Springer Spaniel is one of the breeds affected by PRA and a mutation in the RPGRIP1 gene (CORD1 PRA mutation) was found as a causal mutation in the breed. This DNA test has been offered since 2007 to the English Springer Spaniel breed to help reduce the prevalence of the CORD1 mutation in the population.

Since the CORD1 PRA mutation was discovered, it has been difficult to explain why some genetically affected dogs lose their eyesight rapidly, at a very young age, yet others do not go blind until much later on, or even not at all throughout their lifetimes. There have also been some dogs clinically diagnosed with PRA that are not genetically affected for the CORD1 mutation, indicating that the English Springer Spaniel is one of a number of breeds carrying more than one genetic mutation for PRA.

Next stage of PRA research in the English Springer Spaniel

We are interested in receiving DNA samples from any English Springer Spaniel that has been diagnosed with PRA by a veterinary ophthalmologist but is genetically clear of the CORD1 mutation. For more information and/or to submit your sample, please contact Rebekkah at rebekkah.hitti@aht.org.uk.

PRA in the Lhasa Apso

With the help of the Lhasa Apso breed council and their passionate Lhasa Apso owners, new investigations are underway aiming to identify the genetic cause of PRA in the breed. A genome-wide association study has been conducted using a set of PRA cases and older clear control Lhasa Apsos. This approach scans the DNA for genetic markers to find regions of DNA that are statistically associated with the disease. This data is being analysed and any regions of interest will be followed up in additional Lhasa Apso DNA samples that have been confirmed as affected or clear of PRA.

Do you have a Lhasa Apso that can contribute to our PRA research?

We are still welcoming samples to contribute to this research project to follow up any potential variants we find. If you have a Lhasa Apso fulfilling either of the requirements below, please contact Rebekkah (rebekkah.hitti@aht.org.uk) for more information on how to submit a sample:

PRA affected dogs -Lhasa Apsos affected with PRA, diagnosed by a certified veterinary ophthalmologist, with a referral letter or a BVA eye certificate, or the equivalent if overseas.

PRA unaffected dogs -Lhasa Apsos that are clear of PRA must be over the age of 8 years old with a referral letter or a BVA eye certificate as above, or the equivalent if overseas.

A previous dataset that we have already generated for the Lhasa Apso is still being analysed and will also be used subsequent to the above DNA scan to scrutinise any region that appears to be strongly associated with PRA, to see if we can identify the causative mutation underlying any association signal.

PRA in the Giant Schnauzer

We are currently using a whole genome sequencing approach (reading the entire DNA from an individual) to investigate PRA in the Giant Schnauzer. Data from PRA-affected cases will be compared against older clear Giant Schnauzers to try and identify the casual mutation for PRA in these dogs.

Although PRA does not seem to be highly prevalent and has not been investigated previously in this breed, we are still inviting the submission of samples from Giant Schnauzers that have been diagnosed with PRA by a veterinary ophthalmologist, with a BVA certificate or referral letter, or dogs that have had a recent BVA eye examination and have clear eyes. For more information, please contact Rebekkah (rebekkah.hitti@aht.org.uk).

Samples most needed - Do you have a Giant Schnauzer over the age of six?

To help this research, we need more DNA samples from Giant Schnauzers that are over six years old and have a clear BVA/KC/ISDS eye certificate. To help get these DNA samples, we are offering free BVA/KC/ISDS eye examinations to 14 Giant Schnauzer’s older than six years of age. A DNA cheek swab sample will also be required.

If you think your dog could help, please contact Rebekkah at rebekkah.hitti@aht.org.uk for more information and to submit a DNA sample. Eye examination reimbursements will be made on a first come first served basis and require an eye examination to be carried out by a BVA Panellist.

PRA breeds involved in GDG project

The Kennel Club Genetics Centre at the Animal Health Trust launched the Give a Dog a Genome project in January 2016. So far 75 breeds have signed up to the project which will equip us with a large genome bank to improve canine health. For more information on the project, please follow this link to the Give a Dog a Genome page.

From the breeds partaking in the project, a number listed PRA as one of the top three health concerns. PRA cases from the following breeds will be sent off for whole genome sequencing to analyse and hopefully identify what is causing PRA in each of these breeds:

Gordon Setter

Papillon

Picardy Sheepdog

Shetland Sheepdog

Tibetan Spaniel

Tibetan Terrier

Do you have a dog that has been diagnosed with PRA?

In addition to the breeds listed above we will investigate the genetics of PRA in any other breeds for which we can collect sufficient DNA samples. We collect and store, for future use, DNA from dogs of any breed affected with PRA.

Which dogs can contribute to the AHT’s PRA research?

There are two types of dog that are useful to our research:

Dogs of any breed that have been diagnosed as AFFECTED with PRA.

Dogs of any breed over the age of eight years that have had a current eye examination by a veterinary ophthalmologist and are CLEAR of PRA.

The Animal Health Trust is a veterinary charity, based in Suffolk, which offers clinical referral services and diagnostic testing for horses, dogs and cats in East Anglia, across the UK and internationally. Through its research programmes it develops new diagnostic tests, treatments and vaccines to help thousands of animals.